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. 2014 Dec;231(23):4561-8.
doi: 10.1007/s00213-014-3605-3. Epub 2014 May 25.

Wistar rats acquire and maintain self-administration of 20 % ethanol without water deprivation, saccharin/sucrose fading, or extended access training

Affiliations

Wistar rats acquire and maintain self-administration of 20 % ethanol without water deprivation, saccharin/sucrose fading, or extended access training

E Augier et al. Psychopharmacology (Berl). 2014 Dec.

Abstract

Rationale: Operant self-administration (SA) is an important model of motivation to consume ethanol (EtOH), but low rates of voluntary consumption in rats are thought to necessitate water deprivation and saccharin/sucrose fading for acquisition of responding.

Objectives: Here, we sought to devise an effective model of SA that does not use water deprivation or saccharin/sucrose fading.

Methods: First, we tested if Wistar rats would acquire and maintain SA behavior of 20 % EtOH under two conditions, water deprivation (WD) and non-water deprivation (NWD). Second, we tested the efficacy of our SA procedure by confirming a prior study which found that the NK1 antagonist L822429 specifically blocked stress-induced reinstatement of EtOH seeking but not SA. Finally, we assessed the effect of naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress EtOH SA in rodents.

Results: Lever presses (LPs) and rewards were consistent with previous reports that utilized WD and saccharin/sucrose fading. Similar to previous findings, we found that L822429 blocked stress-induced reinstatement but not baseline SA of 20 % EtOH. Moreover, naltrexone dose-dependently decreased alcohol intake and motivation to consume alcohol for rats that are self-administering 20 % EtOH.

Conclusions: Our findings provide a method for voluntary oral EtOH SA in rats that is convenient for experimenters and eliminates the potential confound of sweeteners in EtOH-operant SA studies. Unlike models that use intermittent access to 20 % EtOH, this method does not induce escalation, and based on pharmacological experiments, it appears to be driven by the positive reinforcing effects of EtOH.

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Figures

Fig. 1
Fig. 1
a: Average active lever presses completed during 30 minute SA sessions (FR1) of 20% EtOH for water deprived (WD) and non-water deprived (NWD) rats b: Average rewards during 30 minute SA sessions (FR1) of 20% EtOH for water deprived (WD) and non-water deprived (NWD) rats (** = p<0.01). c: Number of rewards earned during one 30 minute SA session versus BEC (mg/dl) (R2=0.59, p= 0.0009)
Fig 2
Fig 2
a: Mean active lever presses (± SEM) completed during a 30 minute SA session (FR1) of 20% EtOH following either vehicle (n=16) or L822429 treatment (15 or 30 mg/kg) in Wistar rats (n=8 for each dose) (p=0.86). b: Mean rewards (±SEM) earned during a 30 minute SA session (FR1) of 20% EtOH following either vehicle (n=16) or L822429 treatment (15 or 30 mg/kg) in Wistar rats (n=8 for each dose) (p=0.77). c: Mean baseline, extinction, and reinstatement active lever presses (± SEM) following either vehicle or L822429 treatment (30 mg/kg) in Wistar rats (n=8 in each group) (**= p<0.01).
Fig. 3
Fig. 3
a: Mean active lever presses (± SEM) completed during a 30 minute SA session (FR3) of 20% EtOH following either saline or naltrexone treatment (0.1, 0.3 or 1 mg/kg) in Wistar rats (n=16) (** = p<0.01, *** = p<0.001) b: Mean rewards (± SEM) earned during a 30 minute SA session (FR3) of 20% EtOH following either saline or naltrexone treatment (0.1, 0.3 or 1 mg/kg) in Wistar rats (n=16) (** = p<0.01, *** = p<0.001). c: Mean breakpoint (± SEM) reached during a PR session of 20% EtOH following either saline or naltrexone treatment (1 mg/kg) in Wistar rats (n=16) (* = p<0.05)

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